Sen'kova Alexandra V, Mironova Nadezhda L, Patutina Olga A, Ageeva Tatyana A, Zenkova Marina A
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Science, Lavrentiev Avenue 8, Novosibirsk 630090, Russia ; Novosibirsk State Medical University, Krasnyi Prospect 52, Novosibirsk 630091, Russia.
ISRN Oncol. 2012;2012:721612. doi: 10.5402/2012/721612. Epub 2012 Nov 29.
Antitumor therapy of hematological malignancies is impeded due to the high toxicity of polychemotherapy toward liver and increasing multiple drug resistance (MDR) of tumor cells under the pressure of polychemotherapy. These two problems can augment each other and significantly reduce the efficiency of antineoplastic therapy. We studied the combined effect of polychemotherapy and upregulated MDR of lymphosarcoma RLS(40) onto the liver of experimental mice using two treatment schemes. Scheme 1 is artificial: the tumor was subjected to four courses of polychemotherapy while the liver of the tumor-bearing mice was exposed to only one. This was achieved by threefold tumor retransplantation taken from animals subjected to chemotherapy into intact animals. Scheme 2 displays "real-life" status of patients with MDR malignancies: both the tumor and the liver of tumor-bearing mice were subjected to three sequential courses of polychemotherapy. Our data show that the strengthening of MDR phenotype of RLS(40) under polychemotherapy and toxic pressure of polychemotherapy itself has a synergistic damaging effect on the liver that is expressed in the accumulation of destructive changes in the liver tissue, the reduction of the regeneration capacity of the liver, and increasing of Pgp expression on the surface of hepatocytes.
由于多药化疗对肝脏毒性高，且在多药化疗压力下肿瘤细胞的多药耐药性（MDR）不断增加，血液系统恶性肿瘤的抗肿瘤治疗受到阻碍。这两个问题会相互加剧，显著降低抗肿瘤治疗的效率。我们使用两种治疗方案研究了多药化疗和上调淋巴肉瘤RLS(40)的MDR对实验小鼠肝脏的联合作用。方案1是人为设定的：肿瘤接受四个疗程的多药化疗，而荷瘤小鼠的肝脏仅接受一个疗程的化疗。这是通过将接受化疗的动物的肿瘤进行三次再移植到未受影响的动物体内实现的。方案2展示了MDR恶性肿瘤患者的“实际情况”：荷瘤小鼠的肿瘤和肝脏都接受三个连续疗程的多药化疗。我们的数据表明，在多药化疗和多药化疗本身的毒性压力下，RLS(40)的MDR表型增强对肝脏具有协同损害作用，表现为肝组织中破坏性变化的积累、肝脏再生能力的降低以及肝细胞表面Pgp表达的增加。
